DR55.1 DataRelease
Release Date: April 2025
New Studies: 34
Updated Studies: 21
New Studies
| SDY2510: Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) | ||||||||||||||||||
| Status: | New | |||||||||||||||||
| Description: | This is a prospective, multicenter, observational cohort study to assess short and long-term clinical outcomes and immune responses after SARS-CoV-2 infection and/or MIS-C in children (defined as individuals who have not reached their 21st birthday at the time of enrollment). Subjects will be identified through active recruitment measures within hospitals and through ambulatory and laboratory-based databases of SARS-CoV-2 positive children. The study will enroll a minimum of 250 subjects from a diverse racial/ethnic background, from approximately 20 medical centers in the United States. The study period is 18 months; 6-month accrual period, and 12-month follow up period. Standard Follow-Up: All subjects meeting eligibility criteria, whether hospitalized or not, and whether presenting with MIS-C or not, will be asked to participate in a comprehensive follow-up according to the standard schedule of events. Limited Follow-Up: In rare circumstances it may not be possible to obtain complete follow up on consented subjects (i.e. they will be unable to participate in the full schedule of events). Examples might be infants and small children in whom adequate blood volumes will be hard to obtain, or subject who live remotely from the study site in whom it may not be possible to attend regular in-person visits. These subjects will complete as many of the study assessments as possible, e.g. review of the electronic health record (EHR), nasal and saliva samples for viral surveillance, and the health-related quality of life questionnaires, but may not have any (or complete) blood collection for immunology core lab or cardiopulmonary studies for core lab. These subjects will be characterized as having “limited follow up” and will contribute, at a minimum, clinical outcomes for the study. Non-Consented Subjects: To minimize bias that may be generated for non-consented children (e.g. early death prior to consent), the study coordinator will complete a screening form for every potentially eligible patient and will indicate the reason(s) for ineligibility if the patient does not meet study entry criteria. No patient identifiers will be entered into this log. In addition, for hospitalized patients fulfilling inclusion criteria, but where consent was not be obtained, a limited dataset will be entered into the database via a unique CRF that collects vital information including demographics, presenting clinical features, key laboratory results and outcome during hospitalization. MIS-C subjects with previously banked biospecimens: Certain hospitalized subjects with MIS-C or severe COVID-19 diagnosed in the weeks prior to the onset of the PRISM study have biospecimens banked under existing IRB protocols at PRISM study immunology core laboratories. Because of the rare nature of MIS-C it is important to capture these subjects. Therefore, these subjects will be eligible for consent into PRISM and will be followed prospectively after informed consent has been obtained. These subjects must, at a minimum, be available for the scheduled 6-month visit corresponding to the timing of the primary clinical endpoint. Any missed study visits prior to obtaining informed consent in PRISM will not be considered as protocol deviations. EHR data will be collected retrospectively. Samples will be distributed to the immunologic core laboratories and the viral surveillance laboratory according to the Schedule of Events and the PRISM Study Laboratory Manual. Results from the Stanford- and Cornell-coordinated laboratories will be compared where applicable. Samples will be shared to evaluate reproducibility and confirm important results. This design allows the immunology core laboratories to pursue both common and distinct investigations and reduces the risks of systematic errors leading to erroneous conclusions. | |||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3FRDWDDJ9 | |||||||||||||||||
| Subjects: | 597 | |||||||||||||||||
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| Publications: | None | |||||||||||||||||
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| Assays: | None | |||||||||||||||||
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| SDY2534: Human TFH responses to malaria specific antigen using a Kenyan cross sectional study | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Peripheral blood mononuclear cells (PBMCs) were collected from fourteen 7-years old children and from fifteen adults aged from 19 to 30 years from Western Kenya. These cells were frozen down and kept in liquid nitrogen until use. After thawing, they rested overnight and were placed in culture under the following condition: no stimulation, stimulation with PfSEA-1A antigen, stimulation with PfGARP antigen and stimulation with SEB. After 6 hours, cells from each condition were stained with a spectral flow cytometry panel which included: CCR6-BV421 (RRID: AB_2561356), CD14-Pacific Blue (RRID: AB_830689), CD19-Pacific Blue (RRID: AB_2073118), CCR7-BV480 (RRID: AB_2739502), IFNγ-BV510 (RRID: AB_2563883), CD127-BV570 (RRID: AB_10900064), CD45RA-BV605 (RRID: AB_2563814), PD1-BV650 (RRID: AB_2738746), CXCR3-BV711 (RRID: AB_2563533), CD25-BV750 (RRID: AB_2871896), CXCR5-BV785 (RRID: AB_2629528), Bcl6-AF488 (RRID: AB_10716202), CD3-Spark Blue 550 (RRID: AB_2819985), CD8-PerCP-Cy5.5 (RRID: AB_2044010), IL21-PE (RRID: AB_2249025), IL4-PE-Dazzle (RRID: AB_2564036), CD4-PE-Cy5 (RRID: AB_314078), ICOS-PE-Cy7 (RRID: AB_10643411), cMAF-eFluor 660 (RRID: AB_2574388), CD40L-AF700 (RRID: AB_2750053), and Zombie NIR (BioLegend cat# 423106) for Live/Dead staining. Data was acquired on a Cytek Aurora with 4-lasers (Violet, Blue, Yellow/Green and Red) under SpectroFlo® software (Cytek) using compensation for unmixing and fluorescence-minus-one controls. From the same participants, using plasma, we run an in-house made Pf malaria serological panel to screen the presence of anti-Pf antigens antibodies. To measure plasma IgG antibody levels to PfSEA-1A and PfGARP, we used a Luminex bead-based suspension assay. In addition, Pf exposure was determined using recombinant proteins to blood-stage malaria antigens: apical membrane antigen 1 (AMA1) and merozoite surface protein (MSP1), HRP2, CelTos, CSP (gifts from Sheetji Dutta, Evelina Angov, and Elke Bergmann from the Walter Reed Army Institute of Research). Briefly, 100μg of each antigen or BSA (Sigma), as a background control, were coupled to ~12x106 non-magnetic microspheres (BioRad carboxylated beads) and then incubated with study participant plasma (spun down 10,000g for 10 mins and diluted at 1:100 in the assay dilution buffer) for 2 hrs, followed by incubation with biotinylated anti-human IgG (BD #555785) diluted 1:1000 for 1hr and streptavidin (BD #554061) diluted 1:1000 for 1 hr following the manufacturer's instructions. The mean fluorescence intensity (MFI) of each conjugated bead (minimum of 50 beads per antigen) was quantified on a FlexMap3D Luminex multianalyte analyzer (Xponent software). Results are reported as antigen-specific MFI after subtracting the BSA value for each individual, since background levels can vary between individuals. Finally we also run Pf qPCR from whole blood from all the participant to assess if they were under an ongoing Pf malaria asymptomatic infection. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3A4ZTNPYI | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Publications: | None | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY2823: The Sound Life Project Healthy Adult Immunotypes | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Understanding the variability of immune cell composition and responsiveness in health is critical to define changes that predict and explain immune-associated diseases like autoimmunity and cancer. Here, we enrolled and comprehensively phenotyped a cohort of 100 healthy adults aged 25 to 35 and 55 to 65 years who were longitudinally followed for 10 visits over 2 years. Using mass cytometry features that remain stable within but differ between individuals, we identified four longitudinally stable immunotypes that distinguished the individuals in this cohort. We characterized these immunotypes using whole blood RNA sequencing, Olink proteomic profiling, and whole blood ex vivo stimulation. While CMV seropositivity, age, and sex are known to influence the immune landscape; notably, the four immunotypes were not solely determined by these factors. A CMV dominant immunotype, where 70% of individuals were CMV positive, exhibited exaggerated traditional markers of CMV positivity but also features unrelated to CMV positivity, including a reduction in B cell frequency and transcripts. We show that serological response to influenza vaccination is consistent across immunotype, while response to ex vivo stimulation with SEB or LPS varies by immunotype. Finally, we identify an immunotype comprised of young females with unusually high LPS responsiveness, mature neutrophil frequency, and increased inflammatory markers, characteristics more expectedly seen in older individuals. Our findings establish that healthy individuals exhibit shared immunotypes that are stable over time and influence response to innate signals. Future work will illuminate whether immunotypes may explain immune disease risk or likelihood of response to immune therapies. | ||||||||||||
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| DOI: | 10.21430/M3V8GRIGH8 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Publications: | None | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY2976: TCR delta chain repertoire sequencing | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | A case-control study for coeliac disease, where TCR delta chain repertoires are profiled in bulk. 2 cohorts are used in training and testing of TCR repertoire classification models, which include duodenal biopsy samples from 139 and 23 donors respectively. We compared kmer-based TCR repertoire representations to understand the effect of amino acid similarity information on XGBoost classification performance in general, and for coeliac disease status specifically. | |||||||||||||||
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| DOI: | 10.21430/M3PH74QVB2 | |||||||||||||||
| Subjects: | 162 | |||||||||||||||
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| Publications: | None | |||||||||||||||
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| Assays: | None | |||||||||||||||
| Clinical Assessments: | None | |||||||||||||||
| SDY3009: Deep immunological imprinting due to the ancestral spike in the current bivalent COVID-19 vaccine | |||||||||||||||
| Status: | New | ||||||||||||||
| Description: | The investigators conducted an in-depth analysis of antibody profiles from various SARS-CoV-2 vaccine cohorts to study the issue of immunological imprinting caused by the ancestral spike in the current SARS-CoV-2 bivalent mRNA vaccines. | ||||||||||||||
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| DOI: | 10.21430/M3AFLKTLZ4 | ||||||||||||||
| Subjects: | 72 | ||||||||||||||
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| SDY3010: Anitbody landscapes after influenza virus infection or vaccination | |||||||
| Status: | New | ||||||
| Description: | In the vaccine studies (1997, 1998, 2009, 2010) subjected were administered a trivalent influenza vaccine and HAI was measured at days 0 and 28 post-vaccination. | ||||||
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| DOI: | 10.21430/M307A4FVT9 | ||||||
| Subjects: | 394 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY3011: Differential Recognition Infuenza Vaccine Candidates by Human Antibodies | ||||||||||
| Status: | New | |||||||||
| Description: | We determined the structural integrity of an H3N2 COBRA hemagglutinin (HA), TJ5, and we probed the antigenic prole of several H3N2 COBRA HAs by assessing recognition of these immunogens by human B cells from seasonally vaccinated human subjects. Of three recently described COBRA H3 HA antigens (TJ5, NG2, and J4), we determined that TJ5 and J4 HA proteins recognize pre-existing B cells more effectively than NG2 HA and a wild-type Hong Kong/4801/2014 protein. | |||||||||
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| DOI: | 10.21430/M3TI5E2PLG | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY3013: Evolving antibody evasion and receptor affinity of the Omicron BA.2.75 sublineage of SARS-CoV-2 | ||||||||||
| Status: | New | |||||||||
| Description: | Viral receptor affinities and neutralization evasion properties of major BA.2.75 subvariants actively circulating in different regions worldwide were investigated. Binding affinity between hACE2 and each spike of several variants were measured by surface plasmon resonance (SPR). Generated vesicular stomatitis virus (VSV)-pseudotyped viruses were assessed for their neutralization profiles by a panel of mAbs. Structural modeling was conducted to investigate how mutations in subvariants confer resistance or sensitization to mAbs against different epitopes. Neutralization resistance profiles of BA.2.75 subvariants were assessed by sera from four different clinical cohorts. Antigenic cartography was used to visualize neutralization results. | |||||||||
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| DOI: | 10.21430/M3NG4MHIPW | |||||||||
| Subjects: | 54 | |||||||||
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| SDY3014: Enhanced CD4 T Cell Response with R-DOTAP Lipid Nanoparticles | ||||||||||
| Status: | New | |||||||||
| Description: | Mice were immunized with B/Mal/04 HA protein emulsified in R-DOTAP adjuvant. CD4 T cellular immunity response was assessed post-vaccination by IFN-g and IL-2 ELISpot and ELISA assays. | |||||||||
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| DOI: | 10.21430/M3WNLL6BPH | |||||||||
| Subjects: | 80 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY3015: Flu-COVID combination vaccine and immune response | |||||||
| Status: | New | ||||||
| Description: | Healthy mice were vaccinated with a combination flu-COVID vaccine, COBRA H1 and H3, and antibody response was analyzed after being challenged with virus. The combination vaccine is being tested to administer one seasonal vaccine as opposed to two. | ||||||
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| DOI: | 10.21430/M35PZ7ECKM | ||||||
| Subjects: | 105 | ||||||
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| Assays: | None | ||||||
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| SDY3016: Vaccination History, BMI, Age and Gene Expression Predict Influenza Vaccination Outcomes | |||||||||||||
| Status: | New | ||||||||||||
| Description: | A number of factors influence vaccination effectiveness, including age, sex, and comorbidities. A transcriptome analysis was performed via RNA sequencing. The genes with immunological functions are increased in expression in individuals with high pre-existing immunity. Based on the transcriptome analysis, the set of genes can be used to predict a vaccine response. | ||||||||||||
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| DOI: | 10.21430/M3KA9EZEP8 | ||||||||||||
| Subjects: | 275 | ||||||||||||
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| Assays: | None | ||||||||||||
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| SDY3018: Serum Immunoglobulin Isotype Patterns in Mice and Humans | |||||||
| Status: | New | ||||||
| Description: | Evaluation of serum immunoglobulin isotype patterns in male and female mice. WT female mice were compared to estrogen receptor knockout mice, unmanipulated female mice were compared to ovariectomized mice. Female mice were supplemented with estrogen and male mice were supplemented with testosterone. In the human study, data were examined from three sets of previously described male and female human blood samples. | ||||||
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| DOI: | 10.21430/M3NSDIWYC4 | ||||||
| Subjects: | 166 | ||||||
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| Assays: | None | ||||||
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| SDY3019: Medical Mistrust and SARS-CoV-2 Antibody Testing Among African Americans and White Americans | ||||||||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||||||||
| Description: | Recent research suggests that in addition to structural barriers (e.g., access), psychosocial factors can influence uptake of COVID-19 tools and treatments. However, less is known about racial differences in this potential link for SARS-CoV-2 antibody We evaluated whether medical mistrust alters receptivity to SARS-CoV-2 antibody testing, and whether this influence differs across race. African Americans (N = 306) and White Americans (N = 205) were recruited from a Midwest urban community for an online study about COVID-19 and SARS-CoV-2 antibody testing. Participants completed the Group-Based Medical Mistrust Scale and then viewed educational videos about the SARS-CoV-2 virus, antibodies, and antibody testing. Participants reported their receptivity to antibody testing using measures grounded in the Theory of Planned Behavior (TPB) (attitudes, normative beliefs, perceived behavioral control, and intentions). Medical mistrust was significantly higher among African Americans than White Americans, although there were no race differences in receptivity to antibody testing. Multiple regression analyses showed that higher medical mistrust was associated with lower receptivity to antibody testing across all TPB measures. A significant race x medical mistrust interaction suggested that medical mistrust was more strongly associated with less favorable antibody testing attitudes among White Americans than African Americans. Results suggest that medical mistrust may be a general psychosocial barrier to antibody testing. However, despite being higher among African Americans, mistrust may exert a stronger influence on receptivity toward antibody testing among White Americans, highlighting a need to consider medical mistrust as a barrier to health behavior responses across races. | |||||||||||||||||||||||||||
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| DOI: | 10.21430/M3UX3FYPIQ | |||||||||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||||||||
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| Assays: | None | |||||||||||||||||||||||||||
| Clinical Assessments: | None | |||||||||||||||||||||||||||
| SDY3024: Influenza virus immune imprinting and outcomes in H5N1 challenged ferrets | |||||||
| Status: | New | ||||||
| Description: | Naive ferrets were inoculated with H3N2 viruses to become pre-immune, then vaccinated with a Hu-CO 2 COBRA vaccine and finally challenged with the avian H5N1 virus to test immune response in comparison to those who were not pre-immune. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3XBMJLGMG | ||||||
| Subjects: | 112 | ||||||
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| Assays: | None | ||||||
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| SDY3025: Obesity affects influenza disease severity and transmission in ferrets | |||||||
| Status: | New | ||||||
| Description: | Investigation of mechanisms of influenza disease severity and trasmission in the context of obesity. Diet-induced ferret were used to explore the impact of obesity on disease pathogenesis, viral transmission, and evolution. | ||||||
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| DOI: | 10.21430/M3RHS9QED5 | ||||||
| Subjects: | 142 | ||||||
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| Assays: | None | ||||||
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| SDY3027: Durability of immune responses to mRNA booster vaccination against COVID-19 | ||||||||||
| Status: | New | |||||||||
| Description: | Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown. We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines. | |||||||||
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| DOI: | 10.21430/M3A47OK2V2 | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY3028: SARS-CoV-2 Serological Investigation of White-Tailed Deer in Northeastern Ohio | ||||||||||
| Status: | New | |||||||||
| Description: | Coronaviruses are known to cross species barriers, and spill over among animals, from animals to humans, and vice versa. SARS-CoV-2 emerged in humans in late 2019. It is now known to infect numerous animal species, including companion animals and captive wildlife species. Experimental infections in other animals have established that many species are susceptible to infection, with new ones still being identified. We have developed an enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, that is both sensitive and specific. It can detect S antibodies in sera at dilutions greater than 1:10,000, and does not cross-react with antibodies to the other coronaviruses tested. We used the S antibody ELISA to test serum samples collected from 472 deer from ten sites in northeastern Ohio between November 2020 and March 2021, when the SARS-CoV-2 pandemic was first peaking in humans in Ohio, USA. Antibodies to SARS-CoV-2 were found in serum samples from every site, with an overall positivity rate of 17.2%; we further compared the viral neutralizing antibody titers to our ELISA results. These findings demonstrate the need to establish surveillance programs to monitor deer and other susceptible wildlife species globally. | |||||||||
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| DOI: | 10.21430/M34FYJM2GT | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY3030: CD4+ T-Cell Epitope Prediction by Combined Analysis of Antigen Conformational Flexibility and Peptide-MHCII Binding Affinity | |||||||||||
| Status: | New | ||||||||||
| Description: | Antigen processing in the class II MHC pathway depends on conventional proteolytic enzymes, potentially acting on antigens in native-like conformational states. CD4+ epitope dominance arises from a competition among antigen folding, proteolysis, and MHCII binding. Protease-sensitive sites, linear antibody epitopes, and CD4+ T-cell epitopes were mapped in plague vaccine candidate F1-V to evaluate the various contributions to CD4+ epitope dominance. Using X-ray crystal structures, antigen processing likelihood (APL) predicts CD4+ epitopes with significant accuracy for F1-V without considering peptide-MHCII binding affinity. We also show that APL achieves excellent performance over two benchmark antigen sets. The profiles of conformational flexibility derived from the X-ray crystal structures of the F1-V proteins, Caf1 and LcrV, were similar to the biochemical profiles of linear antibody epitope reactivity and protease sensitivity, suggesting that the role of structure in proteolysis was captured by the analysis of the crystal structures. The patterns of CD4+ T-cell epitope dominance in C57BL/6, CBA, and BALB/c mice were compared to epitope predictions based on APL, MHCII binding, or both. For a sample of 13 diverse antigens, the accuracy of epitope prediction by the combination of APL and I-Ab-MHCII-peptide affinity reached 36%. When MHCII allele specificity was also diverse, such as in human immunity, prediction of dominant epitopes by APL alone reached 42% when using a stringent scoring threshold. Because dominant CD4+ epitopes tend to occur in conformationally sFig antigen domains, crystal structures typically are available for analysis by APL, and thus, the requirement for a crystal structure is not a severe limitation. | ||||||||||
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| DOI: | 10.21430/M3W59NUG02 | ||||||||||
| Subjects: | 0 | ||||||||||
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| SDY3031: Neutralizing antibody response to SARS-CoV-2 bivalent mRNA vaccine in SIV-infected rhesus macaques: Enhanced immunity to XBB subvariants by two-dose vaccination | |||||||
| Status: | New | ||||||
| Description: | The evolution of SARS-CoV-2 paired with immune imprinting by prototype messenger RNA (mRNA) vaccine has challenged the current vaccination efficacy against newly emerged Omicron subvariants. In our study, we investigated a cohort of macaques infected by SIV and vaccinated with two doses of bivalent Pfizer mRNA vaccine containing wildtype and BA.5 spikes. Using a pseudotyped lentivirus neutralization assay, we determined neutralizing antibody (nAb) titers against new XBB variants, i.e., XBB.1.5, XBB.1.16, and XBB.2.3, alongside D614G and BA.4/5. We found that compared to humans vaccinated with three doses of monovalent mRNA vaccine plus a bivalent booster, the monkeys vaccinated with two doses of bivalent mRNA vaccines exhibited relatively increased titers against XBB subvariants. Of note, SIV-positive dam macaques had reduced nAb titers relative to SIV-negative Dams,. Additionally, SIV positive Dams, that received antiretroviral therapy had lower nAb titers than untreated Dams,. Our study underscores the importance of reformulating the COVID-19 vaccine to better protect against newly emerged XBB subvariants as well as the need for further investigation of vaccine efficacy in individuals living with HIV-1. | ||||||
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| DOI: | 10.21430/M3NXLV1E8G | ||||||
| Subjects: | 0 | ||||||
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| SDY3032: Inhibition of mRNA nuclear export promotes SARS-CoV-2 pathogenesis | |||||||||||||||||
| Status: | New | ||||||||||||||||
| Description: | The nonstructural protein 1 (Nsp1) of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virulence factor that targets multiple cellular pathways to inhibit host gene expression and antiviral response. However, the underlying mechanisms of the various Nsp1-mediated functions and their contributions to SARS-CoV-2 virulence remain unclear. Among the targets of Nsp1 is the mRNA (messenger ribonucleic acid) export receptor NXF1-NXT1, which mediates nuclear export of mRNAs from the nucleus to the cytoplasm. Based on Nsp1 crystal structure, we generated mutants on Nsp1 surfaces and identified an acidic N-terminal patch that is critical for interaction with NXF1-NXT1. Photoactivatable Nsp1 probe reveals the RNA Recognition Motif (RRM) domain of NXF1 as an Nsp1 N-terminal binding site. By mutating the Nsp1 N-terminal acidic patch, we identified a separation-of-function mutant of Nsp1 that retains its translation inhibitory function but substantially loses its interaction with NXF1 and reverts Nsp1-mediated mRNA export inhibition. We then generated a recombinant (r)SARS-CoV-2 mutant on the Nsp1 N-terminal acidic patch and found that this surface is key to promote NXF1 binding and inhibition of host mRNA nuclear export, viral replication, and pathogenicity in vivo. Thus, these findings provide a mechanistic understanding of Nsp1-mediated mRNA export inhibition and establish the importance of this pathway in the virulence of SARS-CoV-2. | ||||||||||||||||
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| DOI: | 10.21430/M3Z4MVPHEH | ||||||||||||||||
| Subjects: | 0 | ||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||
| SDY3033: Compartment-specific antibody correlates of protection to SARS-CoV-2 Omicron in macaques | ||||||||||
| Status: | New | |||||||||
| Description: | Antibodies represent a primary mediator of protection against respiratory viruses. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are poorly understood. Here we show that antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, NAbs were the strongest correlate of protection and linked to spike-specific binding antibodies and other extra-NAb functions that create a larger protective network. In bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal spike-specific immunoglobulin (Ig)G, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites | |||||||||
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| DOI: | 10.21430/M352BAIYQA | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY3034: Gender disparities in symptomology of COVID-19 among adults in Arkansas | ||||||||||
| Status: | New | |||||||||
| Description: | Only a few studies and reports assessing the natural history and symptomatology for COVID-19 by gender have been reported in literature to date. Thus, the objective of this study was to examine patterns in symptomology of COVID-19 by gender among a diverse adult population in Arkansas. Data on COVID-19 symptoms was collected at day of testing, 7th day and 14th day among participants at UAMS mobile testing units throughout the state of Arkansas. Diagnosis for SARS-CoV-2 infection was confirmed via nasopharyngeal swab and RT-PCR methods. Data analysis was conducted using Chi-square test and Poisson regression to assess the differences in characteristics by gender. A total of 60,648 community members and patients of Arkansas received RT-PCR testing. Among adults testing positive, we observed a statistically significant difference for fever (p < 0.001) and chills (p = 0.04). Males were more likely to report having a fever (22.6% vs. 17.1%; p < 0.001) and chills (14.9% vs. 12.6%; p = 0.04) compared to females. Among adults testing negative, females were more likely to report each symptom than males. To conclude, we observed a greater prevalence of certain symptoms such as fever and chills among men testing positive for COVID-19, compared to women during the time of testing. These differences elucidate the important issue of rapidly emerging health disparities during the COVID-19 pandemic. | |||||||||
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| DOI: | 10.21430/M3CGHCUJP2 | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY3035: Analytical measuring interval, linearity, and precision of serology assays for detection of SARS-CoV-2 antibodies according to CLSI guidelines | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Serology testing is commonly used to evaluate the immunogenicity of COVID-19 vaccines and measure antibodies as a marker of previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, four laboratory-developed serology enzyme-linked immunosorbent assays (SARS-CoV-2 anti-Spike and anti-Nucleocapsid immunoglobin G [IgG] and immunoglobin M [IgM]) calibrated to the WHO International Standard 20/136 were validated via analytical measuring interval (limit of blank [LOB], limit of detection [LOD], and limit of quantification [LOQ]), linearity, and precision according to the Clinical and Laboratory Standards Institute (CLSI) guidelines EP17-A2, EP06 2nd Edition, and EP05-A3. For Spike IgG, LOB was 3.0 binding antibody units per milliliter (BAU/mL), LOD was 4.1 BAU/mL, and LOQ was 27.1 BAU/mL. For Nucleocapsid IgG, LOB was 1.9 BAU/mL, LOD was 3.2 BAU/mL, and LOQ was 24.6 BAU/mL. For Spike IgM, LOB was 57.1 BAU/mL, LOD was 69.0 BAU/mL, and LOQ was 113.5 BAU/mL. For Nucleocapsid IgM, LOD was 242.2 BAU/mL, LOD was 289.9 BAU/mL, and LOQ was 572.4 BAU/mL. Each assay displayed good linearity (max % deviation from linearity (≥LOQ) = 10.7%). The result of within-run repeatability evaluation for medium positive samples was 7.7% for Spike IgG, 4.6% for Nucleocapsid IgG, 7.5% for Spike IgM, and 10.1% for Nucleocapsid IgM. The total precision, including medium positive sample variability across 20 days, three reagent kits, and two operators, was 13.5% for Spike IgG, 14.5% for Nucleocapsid IgG, 17.6% for Spike IgM, and 16.2% for Nucleocapsid IgM. The assays were successfully validated following the applicable CLSI guidelines. All assays met the ±20% deviation from linearity and the ±20% coefficient of variation specification for precision and repeatability. | ||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M36F925DT2 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY3036: SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections. | ||||||||||||
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| DOI: | 10.21430/M32BT6ZQKP | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY3037: Structurally Convergent Antibodies Derived from Different Vaccine Strategies Target the Influenza HA Anchor Epitope with a Subset of VH3 and VK3 Genes. | ||||||||||
| Status: | New | |||||||||
| Description: | Here, the investigators analyzed antibodies that were elicited with different vaccine strategies from different individuals from previous studies. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3IYFDLWDH | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY3038: Beta-spike-containing boosters induce robust and functional antibody responses to SARS-CoV-2 in macaques primed with distinct vaccines | |||||||||||||
| Status: | New | ||||||||||||
| Description: | The reduced effectiveness of COVID-19 vaccines due to the emergence of variants of concern (VOCs) necessitated the use of vaccine boosters to bolster protection against disease. However, it remains unclear how boosting expands protective breadth when primary vaccine platforms are distinct and how boosters containing VOC spike(s) broaden humoral responses. Here, we report that boosters composed of recombinant spike antigens of ancestral (prototype) and Beta VOCs elicit a robust, pan-VOC, and multi-functional humoral response in non-human primates largely independent of the primary vaccine series platform. Interestingly, Beta-spike-containing boosters stimulate immunoglobulin A (IgA) with a greater breadth of recognition in protein-primed recipients when administered with adjuvant system 03 (AS03). Our results highlight the utility of a component-based booster strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for broad humoral recognition, independent of primary vaccine series. This is of high global health importance given the heterogeneity of primary vaccination platforms distributed. | ||||||||||||
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| DOI: | 10.21430/M3K4HFMGV6 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY3039: Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors. Additionally, ORF6 inhibits cellular mRNA export, resulting in the remodeling of the host cell proteome, and regulates viral protein expression. Interestingly, the ORF6:D61L mutation that emerged in the Omicron BA.2 and BA.4 variants exhibits reduced interactions with Nup98-Rae1 and consequently impairs immune evasion. Our findings highlight the role of ORF6 in antagonizing innate immunity and emphasize the importance of studying the immune evasion strategies of SARS-CoV-2. | ||||||||||||
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| DOI: | 10.21430/M3T8X0ZWKR | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY3040: High dose inactivated influenza virus vaccine antibody response | ||||||||||
| Status: | New | |||||||||
| Description: | Antibody Response comparison between high dose (HD) and standard dose (SD) vaccine recipients in a multiyear human vaccination cohort study. Bayesian multilevel regression models were used for main results to predict the outcome of each individual in the study and estimate the effect of dose. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3DONLP073 | |||||||||
| Subjects: | 248 | |||||||||
| Study PI, contact: |
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY3042: Single dose IIV vaccine expressing COBRA HA elicits broadly-reactive and long-lasting protection | |||||||
| Status: | New | ||||||
| Description: | To assess the COBRA-IIV vaccine effectiveness, pre-immune ferrets received either COBRA-WIV or COBRA-SIV vaccinations, followed by an H1N1 influenza virus challenge after 14 weeks. The evaluation involved measuring antibody titers with HAI, assessing protection against direct infection, and monitoring viral shedding and transmission prevention. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3Q2F40L9Z | ||||||
| Subjects: | 72 | ||||||
| Study PI, contact: |
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| Assays: | None | ||||||
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| SDY3043: The assessment of an immune response to repeated influenza vaccination in a multiyear cohort. | |||||||
| Status: | New | ||||||
| Description: | Computational data analysis from a cohort of 386 individuals, who received standard dose of Fluzone IIV vaccine from 2016-2020. The data showed there are interactive effects between the sex, age, and BMI on immune responses in adults. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M31QLQE9V0 | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY3044: Anti-SARS-CoV-2 IgM Antibody Levels Measured by an In-House ELISA in a Convalescent Latin Population Persist over Time and Exhibit Neutralizing Capacity to Several Variants of Concern | ||||||||||
| Status: | New | |||||||||
| Description: | Background: The coronavirus, SARS-CoV-2, is the causative agent for COVID-19, first registered in Wuhan, China and responsible for more than 6 million deaths worldwide. Conclusions: These data indicate that our in-house CovIgM-ELISA is a compatible performing assay for the detection of SARS-CoV-2 infection. | |||||||||
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| DOI: | 10.21430/M3HYQN6RCM | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY3049: Antibody production using COBRA-IIV vaccine | |||||||
| Status: | New | ||||||
| Description: | Healthy mice were vaccinated with a formulated COBRA-IIV Y2 and J4 vaccines adjuvanted with AddaVax, then challenged with H1N1 BS/18 or H3N2 SW/13 viruses. Lung and sera samples were then collected to determine viral titer compared with a mock PBS vaccinated group. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M30FD1JQOC | ||||||
| Subjects: | 381 | ||||||
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| Assays: | None | ||||||
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| SDY3050: COBRA HA and NA vaccine boosts antibody-secreting cells and induces serological response. | |||||||||||
| Status: | New | ||||||||||
| Description: | Healthy mice were pre-immunized and vaccinated with COBRA vaccine containing H2, H5, H7, N1 and N2 antigens. The mice were then challenged with A/Hong Kong/125/2017/H7N9 virus. Samples were collected to assess protective efficacy and immune response. | ||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M30BOPS0TE | ||||||||||
| Subjects: | 38 | ||||||||||
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| SDY3059: Prediction of risk for early or very early preterm births using high-resolution urinary metabolomic profiling | |||||||
| Status: | New | ||||||
| Description: | Preterm birth (PTB) is a serious health problem. PTB complications is the main cause of death in infants under five years of age worldwide. The ability to accurately predict risk for PTB during early pregnancy would allow early monitoring and interventions to provide personalized care | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3BDM7MFH4 | ||||||
| Subjects: | 54 | ||||||
| Study PI, contact: |
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| Assays: | None | ||||||
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Updated Studies
| SDY2045: Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. | ||||||||||||
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| DOI: | 10.21430/M3JP0UEVB0 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2247: Preserved recognition of Omicron spike following COVID-19 messenger RNA vaccination in pregnancy | |||||||
| Status: | Updated | ||||||
| Description: | This study aims to test whether vaccine-induced antibodies raised during pregnancy continue to bind to and leverage Fc receptors to protect against variants of concern including the Omicron variant. The receptor binding domain or whole spike-specific antibody isotype binding titers and Fc gamma receptor binding directed toward variants of concern, including the Omicron variant, were analyzed in pregnant women after receiving the full dose regimen of either the Pfizer/BioNTech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay. Reduced isotype recognition of the Omicron receptor binding domain was observed following administration of either vaccine with relatively preserved, albeit reduced, recognition of the whole Omicron spike by immunoglobulin M and G antibodies. Despite the near complete loss of Fc receptor binding to the Omicron receptor binding domain, Fc receptor binding to the Omicron spike was more variable but largely preserved. Reduced binding titers to the Omicron receptor binding domain aligns with the observed loss of neutralizing activity. Despite the loss of neutralization, preserved, albeit reduced, Omicron spike recognition and Fc receptor binding potentially continue to attenuate disease severity in pregnant women. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3SQTEAH4V | ||||||
| Subjects: | 0 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2376: Coronavirus Disease 2019 Messenger RNA Vaccine Immunogenicity in Immunosuppressed Individuals | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | Individuals on immunosuppressive (IS) therapy have increased mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and delayed viral clearance may lead to new viral variants. IS therapy reduces antibody responses following coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination; however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and nonneutralizing antibody functions in addition to CD4 and CD8 T-cell interferon-γ responses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the standard COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals. | ||||||||||||||||||
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| DOI: | 10.21430/M3XAUTDG0K | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2377: Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Importance: Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited. Objective: To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern. Design, setting, and participants: An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection. Main outcomes and measures: SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine-staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants. Results: This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants. Conclusion and relevance: In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern. | |||||||||||||||
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| DOI: | 10.21430/M39GU9W1LH | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2511: Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and >20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms. Predictive models revealed that IgG binding and ACE2 binding inhibition responses at 1 MPE were positively and C1q complement activity at enrollment was negatively associated with an increased probability of intubation or death from COVID-19 within 3 MPE. Serological antibody measures were more predictive than demographic variables of intubation or death among COVID-19 patients. | ||||||||||||||||||
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| DOI: | 10.21430/M3Q2J8C4ER | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
| Study PI, contact: |
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| Assays: | None | ||||||||||||||||||
| Clinical Assessments: | None | ||||||||||||||||||
| SDY2518: Differences in SARS-CoV-2 Vaccine Response Dynamics Between Class-I- and Class-II-Specific T-Cell Receptors in Inflammatory Bowel Disease | |||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||
| Description: | T-cells specifically bind antigens to induce adaptive immune responses using highly specific molecular recognition, and a diverse T-cell repertoire with expansion of antigen-specific clones can indicate robust immune responses after infection or vaccination. For patients with inflammatory bowel disease (IBD), a spectrum of chronic intestinal inflammatory diseases usually requiring immunomodulatory treatment, the T-cell response has not been well characterized. Understanding the patient factors that result in strong vaccination responses is critical to guiding vaccination schedules and identifying mechanisms of T-cell responses in IBD and other immune-mediated conditions. Here we used T-cell receptor sequencing to show that T-cell responses in an IBD cohort were influenced by demographic and immune factors, relative to a control cohort of health care workers (HCWs). Subjects were sampled at the time of SARS-CoV-2 vaccination, and longitudinally afterwards; TCR Vβ gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant differences in the overall strength of the T-cell response by age and vaccine type. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that Ad26.COV2.S vector vaccine induced Class-I-biased T-cell responses, whereas mRNA vaccine types led to different responses, with mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response compared to BNT162b2. Finally, we showed that these T-cell patterns were consistent with antibody levels from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting that a subset of IBD patients prone to deficiencies in T-cell response may warrant enhanced booster protocols. | ||||||||||||||||||||||||
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| DOI: | 10.21430/M3BGKXJRWY | ||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||
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| SDY2545: Humoral and cellular immune memory to four COVID-19 vaccines | |||||||||||
| Status: | Updated | ||||||||||
| Description: | Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S, and Novavax NVX-CoV2373 were examined longitudinally for 6 months 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though only detectable in 60–67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens. | ||||||||||
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| DOI: | 10.21430/m3yhxnn6ia | ||||||||||
| Subjects: | 0 | ||||||||||
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| SDY2548: Direct comparison of antibody responses to four SARS-CoV-2 vaccines in Mongolia | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Different SARS-CoV-2 vaccines are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four COVID-19 vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V, and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant receptor binding domain (RBD) proteins revealed marked differences in vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control COVID-19 in Mongolia and worldwide. | ||||||||||||
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| DOI: | 10.21430/m3u8jr4ful | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY2554: A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid organ transplant recipients | ||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||
| Description: | Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10 (AU/ml) on the Euroimmun ELISA and >4 Log10 (AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population. | |||||||||||||||||||||
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| DOI: | 10.21430/m3mva0vylw | |||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||||||
| SDY2606: COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and nonpregnant women | ||||||||||
| Status: | Updated | |||||||||
| Description: | Substantial immunological changes occur throughout pregnancy to render the mother immunologically tolerant to the fetus and allow fetal growth. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against pathogens both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contributes to increased susceptibility to particular infections in pregnancy, including more severe coronavirus disease 2019 (COVID-19). Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To define potential changes in vaccine response during pregnancy and lactation, we undertook deep sequencing of the humoral vaccine response in a group of pregnant and lactating women and nonpregnant age-matched controls. Vaccine-specific titers were comparable between pregnant women, lactating women, and nonpregnant controls. However, Fc receptor (FcR) binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared with nonpregnant women after the first vaccine dose, which normalized after the second dose. Vaccine boosting resulted in high FcR-binding titers in breastmilk. These data suggest that pregnancy promotes resistance to generating proinflammatory antibodies and indicates that there is a critical need to follow prime-boost timelines in this vulnerable population to ensure full immunity is attained. | |||||||||
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| DOI: | 10.21430/M3ES2OLH9U | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2612: ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19 | |||||||||||||||
| Status: | Updated | ||||||||||||||
| Description: | Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19. | ||||||||||||||
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| DOI: | 10.21430/M3U2ME6QLL | ||||||||||||||
| Subjects: | 0 | ||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||
| SDY2656: SeroNet Reference Study v2.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | The Reference Study supported development of the National SARS-CoV-2 Serology Standard and assay validation panels. Four Capacity Building Centers (CBCs) collected large volume samples from unvaccinated individuals infected with SARS-CoV-2 and from unvaccinated, uninfected individuals during a visit from 2020-2021 (prior to vaccine availability). Aliquoted serum and PBMCs at 106 M cells per vial, typically at 1ml, from this study may be requested. Demographic and clinical data were collected for 909 participants, 53% of whom were female, and ages ranged from 15 to 80. Detailed information on race and ethnicity was also recorded. The collection is characterized, and includes tertiles of positive test serology results for demographics and other infectious diseases. Sample Testing Samples from these participants were tested with SARS and Non-SARS Molecular and Serology assays. All samples were tested for SARS-CoV-2 positivity by the CBCs using immunoassays and in the FNL Serology Laboratory using an ELISA assay. Additional confirmatory testing was performed by 2 other laboratories. Samples were tested for IgG and IgM antibodies against the SARS-CoV-2 Spike and Nucleocapsid proteins. Positivity for Spike IgG was 67%, spike IgM was 11%, nucleocapsid IgG was 33% and IgM was 16%. Alongside this, many samples were tested for coinfections. Of those tested, 95% were positive for EBV, 47% were positive for CMV. Few samples were tested for HIV and HepB, with a low positivity rate. All samples were tested for seasonal coronavirus and 35% were positive. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3AUTZYP4Q | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Publications: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY2686: Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Purpose: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. Methods: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. Results: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort (P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers (P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower (P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase (P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. Conclusion: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant. | |||||||||||||||
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| DOI: | 10.21430/M3MZOBRIYX | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| SDY2807: Minding the margins: Evaluating the impact of COVID-19 among Latinx and Black communities with optimal qualitative serological assessment tools | ||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||
| Description: | COVID-19 disproportionately affected minorities, while research barriers to engage underserved communities persist. Serological studies reveal infection and vaccination histories within these communities, however lack of consensus on downstream evaluation methods impede meta-analyses and dampen the broader public health impact. To reveal the impact of COVID-19 and vaccine uptake among diverse communities and to develop rigorous serological downstream evaluation methods, we engaged racial and ethnic minorities in Massachusetts in a cross-sectional study (April-July 2022), screened blood and saliva for SARS-CoV-2 and human endemic coronavirus (hCoV) antibodies by bead-based multiplex assay and point-of-care (POC) test and developed across-plate normalization and classification boundary methods for optimal qualitative serological assessments. Among 290 participants, 91.4% reported receiving at least one dose of a COVID-19 vaccine, while 41.7% reported past SARS-CoV-2 infections, which was confirmed by POC- and multiplex-based saliva and blood IgG seroprevalences. We found significant differences in antigen-specific IgA and IgG antibody outcomes and indication of cross-reactivity with hCoV OC43. Finally, 26.5% of participants reported lingering COVID-19 symptoms, mostly middle-aged Latinas. Hence, prolonged COVID-19 symptoms were common among our underserved population and require public health attention, despite high COVID-19 vaccine uptake. Saliva served as a less-invasive sample-type for IgG-based serosurveys and hCoV cross-reactivity needed to be evaluated for reliable SARS-CoV-2 serosurvey results. The use of the developed rigorous downstream qualitative serological assessment methods will help standardize serosurvey outcomes and meta-analyses for future serosurveys beyond SARS-CoV-2. | |||||||||||||||||||||
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| DOI: | 10.21430/M3UXCHOCPN | |||||||||||||||||||||
| Subjects: | 0 | |||||||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||||||
| SDY2808: Hybrid Immunity Shifts the Fc-Effector Quality of SARS-CoV-2 mRNA Vaccine-Induced Immunity | ||||||||||
| Status: | Updated | |||||||||
| Description: | Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data have revealed enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine but were similar to those achieved by naive vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19 and remained higher following the second dose compared to those in naive individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures—either hybrid immunity or two doses of vaccine alone—represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc-effector functions against conserved regions of the virus. | |||||||||
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| DOI: | 10.21430/M3KPXQBM7D | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2837: Identification of a Broadly Protective Seasonal Influenza Vaccination-induced Neuraminidase Antibody | ||||||||||
| Status: | Updated | |||||||||
| Description: | This study explored the potential use of NA as an immunogen for next-generation influenza vaccines by characterizing a vaccine-induced broadly protective monoclonal antibody (mAb) targeting NA. | |||||||||
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| DOI: | 10.21430/M3JTB2XOM2 | |||||||||
| Subjects: | 123 | |||||||||
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| SDY2873: Preclinical evaluation of a universal inactivated influenza B vaccine based on the mosaic hemagglutinin-approach | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Here, the investigators present the preclinical evaluation of a novel universal influenza B virus vaccine based on recombinant mosaic hemagglutinin-based (mHA) viruses. | ||||||||||||
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| DOI: | 10.21430/M3AW2YFNC7 | ||||||||||||
| Subjects: | 600 | ||||||||||||
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| SDY2931: SeroNet Longitudinal Study v4.2.1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated This release contains an update to Biospecimens_v4.2.5 with corrections and additions to specimen receipt to storage data. Added are: a new data dictionary for all the release files, assay SOPs, collection site questionnaires and current release notes. |
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| Description: | The longitudinal serosurveillance study aimed to understand the immune responses to COVID-19 vaccination and SARS-CoV-2 infection. Between 2021 and 2024, four Capacity Building Centers (CBC) collected samples from 3284 participants (3119 are being released), including healthy and immunocompromised populations. Demographic and clinical data were collected for all participants, with 61% female, ages ranged from 0 to > 89 years, and 68% white. Among the 1,806 participants in the general population, 901 were in the Healthy cohort (no reported comorbidities), and 905 were in the Comorbidity cohort (with 1 or more reported comorbidities or chronic conditions). CBCs collected more detailed information from participants in select cohorts (e.g. time of diagnosis, treatment): 824 in Cancer, 162 in IBD, 146 in HIV and 181 transplant recipients. There were on average 4.7 visits per participant. Collection timepoints were strategically aligned for before and after vaccine administration or infection: 30, 60, 90, 120, 180 and 360 days. Vaccination status for participants range from unvaccinated to vaccinated with homologous and heterologous primary series and booster doses. Vaccines used were the licensed mRNA-based vaccines in the large majority of Janssen protein subunit vaccine in X% of cases. Data harmonization was achieved through SeroNet templates submitted by each CBC, validated for business rule compliance, then shipped to the NCI FNL Central Repository | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3AXZXJN91 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY2986: High transmission of endemic human coronaviruses before and during the COVID-19 pandemic in adolescents in Cebu, Philippines | |||||||
| Status: | Updated | ||||||
| Description: | Background: SARS-CoV-2, the causative agent of COVID-19, is a betacoronavirus belonging to the same genus as endemic human coronaviruses (hCoVs) OC43 and HKU1 and is distinct from alpha hCoVs 229E and NL63. In a study of adolescents in the Philippines, we evaluated seroprevalence to the hCoVs, whether pre-pandemic hCoV immunity modulated subsequent risk of SARS-CoV-2 infection, and if SARS-CoV-2 infection affected the transmission of the hCoVs. Methods: From 499 individuals screened in 2021 for SARS-CoV-2 receptor binding domain (RBD) antibodies by enzyme-linked immunosorbent assay (ELISA), we randomly selected 59 SARS-CoV-2 negative and 61 positive individuals for further serological evaluation. We measured RBD and spike antibodies to the four hCoVs and SARS-CoV-2 by ELISA in samples from the same participants collected pre-pandemic (2018-2019) and mid-pandemic (2021), before COVID-19 vaccination. Results: We observed over 72% seropositivity to the four hCoVs pre-pandemic. Binding antibodies increased with age to 229E and OC43, suggesting endemic circulation, while antibody levels was flat across ages for HKU1 and NL63. During the COVID-19 pandemic, antibodies increased significantly to the RBDs of OC43, NL63, and 229E and spikes of all four hCoVs in both SARS-CoV-2 negative and positive adolescents. Those aged 12-15 years old in 2021 had higher antibodies to RBD and spike of OC43, NL63, and 229E than adolescents the same age in 2019, further demonstrating intense transmission of the hCoVs during the pandemic. Conclusions: We observe a limited impact of the COVID-19 pandemic on endemic hCoV transmission. This study provides insight into co-circulation of hCoVs and SARS-CoV-2. | ||||||
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| DOI: | 10.21430/M3YR9AKCII | ||||||
| Subjects: | 0 | ||||||
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| SDY2989: Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection | ||||||||||||||||
| Status: | Updated | |||||||||||||||
| Description: | Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not. | |||||||||||||||
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| DOI: | 10.21430/M3RQPL9W9U | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2994: Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV-2 | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Enveloped viruses co-opt host glycosylation pathways to decorate their surface proteins. As viruses evolve, emerging strains can modify their glycosylation patterns to influence host interactions and subvert immune recognition. Still, changes in viral glycosylation or their impact on antibody protection cannot be predicted from genomic sequences alone. Using the highly glycosylated SARS-CoV-2 Spike protein as a model system, we present a lectin fingerprinting method that rapidly reports on changes in variant glycosylation state, which are linked to antibody neutralization. In the presence of antibodies or convalescent and vaccinated patient sera, unique lectin fingerprints emerge that distinguish neutralizing versus non-neutralizing antibodies. This information could not be inferred from direct binding interactions between antibodies and the Spike receptor-binding domain (RBD) binding data alone. Comparative glycoproteomics of the Spike RBD of wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) variants reveal O-glycosylation differences as a key determinant of immune recognition differences. These data underscore the interplay between viral glycosylation and immune recognition and reveal lectin fingerprinting to be a rapid, sensitive, and high-throughput assay to distinguish the neutralization potential of antibodies that target critical viral glycoproteins. | ||||||||||||
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| DOI: | 10.21430/M3XJOOF2LT | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||